The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT).

Clinical Need: Target Population and Condition

Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population.

Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0.

The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis.

Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a routine basis and that patients are in the therapeutic range only 64% of the time.

Overview of POC INR Devices

POC INR devices offer an alternative to laboratory-based testing and venipuncture, enabling INR determination from a fingerstick sample of whole blood. Independent evaluations have shown POC devices to have an acceptable level of precision. They permit INR results to be determined immediately, allowing for more rapid medication adjustments.

POC devices can be used in a variety of settings including physician offices, ACCs, long-term care facilities, pharmacies, or by the patients themselves through self-testing (PST) or self-management (PSM) techniques. With PST, patients measure their INR values and then contact their physician for instructions on dose adjustment, whereas with PSM, patients adjust the medication themselves based on pre-set algorithms. These models are not suitable for all patients and require the identification and education of suitable candidates.

Potential advantages of POC devices include improved convenience to patients, better treatment compliance and satisfaction, more frequent monitoring and fewer thromboembolic and hemorrhagic complications. Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values, low thromboplastin sensitivity, inability to calculate a mean normal PT, and errors in INR determination in patients with antiphospholipid antibodies with certain instruments. Although treatment satisfaction and quality of life (QoL) may improve with POC INR monitoring, some patients may experience increased anxiety or preoccupation with their disease with these strategies.

Studies where the POC INR results were not used to guide patient management

Method of Review

A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database) was undertaken to identify evidence published from January 1, 1998 to November 25, 2008. Studies meeting the inclusion criteria were selected from the search results. Reference lists of selected articles were also checked for relevant studies.

Anticoagulation control is measured by the percentage of time INR is within the therapeutic range or by the percentage of INR values in the therapeutic range. Due to the differing methodologies and reporting structures used, it was deemed inappropriate to combine the data and estimate whether the difference between groups would be significant. Instead, the results of individual studies were weighted by the number of person-years of observation and then pooled to calculate a summary measure.

Across most studies, patients in the intervention groups tended to have a higher percentage of time and values in the therapeutic target range in comparison to control patients. When the percentage of time in the therapeutic range was pooled across studies and weighted by the number of person-years of observation, the difference between the intervention and control groups was 4.2% for PSM, 7.2% for PST and 6.1% for POC use by health care practitioners. Overall, intervention patients were in the target range 69% of the time and control patients were in the therapeutic target range 64% of the time leading to an overall difference between groups of roughly 5%.

Major Complications and Deaths

There was no statistically significant difference in the number of major hemorrhagic events between patients managed with POC INR monitoring devices and patients managed with standard laboratory testing (OR =0.74; 95% CI: 0.52- 1.04). This difference was non-significant for all POC strategies (PSM, PST, health care practitioner).

Patients managed with POC INR monitoring devices had significantly fewer thromboembolic events than usual care patients (OR =0.52; 95% CI: 0.37 - 0.74). When divided by POC strategy, PSM resulted in significantly fewer thromboembolic events than usual care (OR =0.46.; 95% CI: 0.29 - 0.72). The observed difference in thromboembolic events for PSM remained significant when the analysis was limited to major thromboembolic events (OR =0.40; 95% CI: 0.17 - 0.93), but was non-significant when the analysis was limited to minor thromboembolic events (OR =0.73; 95% CI: 0.08 - 7.01). PST and GP/Nurse strategies did not result in significant differences in thromboembolic events, however there were only a limited number of studies examining these interventions.

No statistically significant difference was observed in the number of deaths between POC intervention and usual care control groups (OR =0.67; 95% CI: 0.41 - 1.10). This difference was non-significant for all POC strategies. Only one study reported on survival with 10-year survival rate of 76.1% in the usual care control group compared to 84.5% in the PSM group (P=0.05).

Summary Results of Meta-Analyses of Major Complications and Deaths in POC INR Monitoring Studies

Patient Satisfaction and Quality of Life

Quality of life measures were reported in eight studies comparing POC INR monitoring to standard laboratory testing using a variety of measurement tools. It was thus not possible to calculate a quantitative summary measure. The majority of studies reported favourable impacts of POC INR monitoring on QoL and found better treatment satisfaction with POC monitoring. Results from a pre-analysis patient and caregiver focus group conducted in Ontario also indicated improved patient QoL with POC monitoring.

Quality of the Evidence

Studies varied with regard to patient eligibility, baseline patient characteristics, follow-up duration, and withdrawal rates. Differential drop-out rates were observed such that the POC intervention groups tended to have a larger number of patients who withdrew. There was a lack of consistency in the definitions and reporting for OAT control and definitions of adverse events. In most studies, the intervention group received more education on the use of warfarin and performed more frequent INR testing, which may have overestimated the effect of the POC intervention. Patient selection and eligibility criteria were not always fully described and it is likely that the majority of the PST/PSM trials included a highly motivated patient population. Lastly, a large number of trials were also sponsored by industry.

Despite the observed heterogeneity among studies, there was a general consensus in findings that POC INR monitoring devices have beneficial impacts on the risk of thromboembolic events, anticoagulation control and patient satisfaction and QoL (ES Table 2).

Using a 5-year Markov model, the health and economic outcomes associated with four different anticoagulation management approaches were evaluated:

Standard care: consisting of a laboratory test with a venipuncture blood draw for an INR;

Healthcare staff testing: consisting of a test with a POC INR device in a medical clinic comprised of healthcare staff such as pharmacists, nurses, and physicians following protocol to manage OAT;

PST: patient self-testing using a POC INR device and phoning in results to an ACC or family physician; and

PSM: patient self-managing using a POC INR device and self-adjustment of OAT according to a standardized protocol. Patients may also phone in to a medical office for guidance.

The primary analytic perspective was that of the MOHLTC. Only direct medical costs were considered and the time horizon of the model was five years - the serviceable life of a POC device.

From the results of the economic analysis, it was found that POC strategies are cost-effective compared to traditional INR laboratory testing. In particular, the healthcare staff testing strategy can derive potential cost savings from the use of one device for multiple patients. The PSM strategy, however, seems to be the most cost-effective method i.e. patients are more inclined to adjust their INRs more readily (as opposed to allowing INRs to fall out of range).

Considerations for Ontario Health System

Although the use of POC devices continues to diffuse throughout Ontario, not all OAT patients are suitable or have the ability to practice PST/PSM. The use of POC is currently concentrated at the institutional setting, including hospitals, ACCs, long-term care facilities, physician offices and pharmacies, and is much less commonly used at the patient level. It is, however, estimated that 24% of OAT patients (representing approximately 32,000 patients in Ontario), would be suitable candidates for PST/PSM strategies and willing to use a POC device.

There are several barriers to the use and implementation of POC INR monitoring devices, including factors such as lack of physician familiarity with the devices, resistance to changing established laboratory-based methods, lack of an approach for identifying suitable patients and inadequate resources for effective patient education and training. Issues of cost and insufficient reimbursement strategies may also hinder implementation and effective quality assurance programs would need to be developed to ensure that INR measurements are accurate and precise.

Conclusions

For a select group of patients who are highly motivated and trained, PSM resulted in significantly fewer thromboembolic events compared to conventional laboratory-based INR testing. No significant differences were observed for major hemorrhages or all-cause mortality. PST and GP/Nurse use of POC strategies are just as effective as conventional laboratory-based INR testing for thromboembolic events, major hemorrhages, and all-cause mortality. POC strategies may also result in better OAT control as measured by the proportion of time INR is in the therapeutic range and there appears to be beneficial impacts on patient satisfaction and QoL. The use of POC devices should factor in patient suitability, patient education and training, health system constraints, and affordability.

Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices.

Methods

Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages.

Results

The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT.

Conclusions

Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum particularly for patients with chronic illness.

Long-term anticoagulation therapy using vitamin K antagonists (VKA) is used in millions of patients worldwide to reduce the risk of thrombotic or thromboembolic events. Control and monitoring of VKA therapy is improved by the regular self-measurement of international normalized ratio (INR) using a home monitoring device. This retrospective analysis of a large cohort of patients in the Netherlands seeks to determine whether the choice of INR monitor could have a clinical impact on patient outcomes.

Methods

The National Thrombosis Service provides medical supervision, training and support to anticoagulant patients eligible for home-monitoring of INR in the Netherlands. Two INR monitors (CoaguChek XS and INRatio2) have been distributed at random to patients since June 2011, and patient self-testing data (INR measurements and other clinical parameters) have been recorded to measure and improve treatment outcomes. The data have been retrospectively analyzed to determine any effect of the choice of monitor. Univariate and multivariate statistical tests are used to assess any differences between groups in terms of efficacy and safety parameters.

Results

Data from 4,326 patients were collated, and 156,507 INR values were included in the analysis. Over half the patients (54.3%) were being treated for atrial fibrillation, and 77.6% were prescribed acenocoumarol. There were few differences between the patient populations using the two different monitors. Anticoagulant control overall was good, with high percentage of time (87.9%) in the appropriate INR range and low incidence of excessively high or low INR values (0.085/month). Minor clinical events related to safety were low (0.78 per patient-year) and showed few differences between monitors. Mortality rates were similar [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.65–1.70].

Conclusion

Self-testing data from a large cohort of patients in the Netherlands suggest that there is no clinically relevant effect of the choice of coagulation monitor (CoaguChek XS or INRatio2) on the time in therapeutic range (TTR), minor or fatal outcomes of long-term anticoagulation management.

Electronic supplementary material

The online version of this article (doi:10.1007/s12325-014-0124-x) contains supplementary material, which is available to authorized users.

Atrial fibrillation (AF) patients frequently require anticoagulation with vitamin K antagonists (VKAs) to prevent thromboembolic events, but their use increases the risk of hemorrhage. We evaluated time spent in therapeutic range (TTR), proportion of international normalized ratio (INR) measurements in range (PINRR), adverse events in relation to INR, and predictors of INR control in AF patients using VKAs.

Patients on VKAs for AF frequently have INRs outside the therapeutic range. While, thromboembolic and hemorrhagic events do occur patients with a therapeutic INR; patients with an INR <2.0 make up many of the cases of thromboembolism, while those >3.0 make up many of the cases of hemorrhage. Managing anticoagulation outside of a clinical trial or anticoagulation clinic is associated with poorer INR control, as is, the initiation of therapy in the VKA-naïve. Patients in Europe/UK have better INR control than those in North America.

A best evidence topic was written according to a structured protocol, to answer the question: ‘In patients taking warfarin, is home self-monitoring of international normalized ratio (INR) safer than clinic-based testing in reducing bleeding, thrombotic events and death?’ Altogether, 268 papers were found using the reported search. Five papers represented the highest level of evidence to answer the clinical question (four systematic reviews with meta-analysis and one meta-analysis). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The principal outcomes of interest were death, major haemorrhage, major thromboembolism, and time (or percentage time) spent within the therapeutic range, compared between self-monitoring/self-management and conventional management. Self-monitoring/self-management was associated with a significantly reduced risk of all-cause mortality of 26–42%. All meta-analyses reported on major thromboembolism, finding significant reductions in risk of ∼50%. One meta-analysis found a 35% reduction in the risk of major haemorrhage, with the other four studies finding no significant difference. Only one study found self-monitoring/self-management to be associated with a significantly greater proportion of time within range, with another finding no significant difference in either the percentage of therapeutic results or in the time within range. The remaining two could not combine data for meta-analysis owing to methodological heterogeneity. We conclude that self-monitoring/self-management appears to be safer than conventional management. It is associated with consistently lower rates of thromboembolism and may also be associated with reduced risk of bleeding and death. This supports the updated guidance from the American College of Chest Physicians, recommending self-management of INR for patients who are both competent and motivated.

Postoperative cognitive dysfunction (POCD) is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD.

Methods

An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12).The standardized mean difference (SMD) and the 95% confidence interval (95%CI) were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis.

Results

A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI]) (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies), and interleukin(IL)-6 (SMD[95%CI]) (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies), but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies).

Conclusions

This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care.

Methods

We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups.

Results

Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001).

Interpretation

Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.

Background: The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring. Patient self management for oral anticoagulation is a model new to the UK. This randomised trial was the first to compare routine primary care management of oral anticoagulation with patient self management.

Aim: To test whether patient self management is as safe, in terms of clinical effectiveness, as primary care management within the UK, as assessed by therapeutic international normalised ratio (INR) control.

Method: Patients receiving warfarin from six general practices who satisfied study entry criteria were eligible to enter the study. Eligible patients were randomised to either intervention (patient self management) or control (routine primary care management) for six months. The intervention comprised two training sessions of one to two hours duration. Patients were allowed to undertake patient self management on successful completion of training. INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed. Patients were advised to perform INR tests every two weeks, or weekly if a dose adjustment was made. Dosage adjustment was undertaken using a simple dosing algorithm.

Results: Seventy eight of 206 (38%) patients were eligible for inclusion and, of these, 35 (45%) declined involvement or withdrew from the study. Altogether, 23 intervention and 26 control patients entered the study. There were no significant differences in INR control (per cent time in range: intervention, 74%; control, 77%). There were no serious adverse events in the intervention group, with one fatal retroperitoneal haemorrhage in the control group. Costs of patient self management were significantly greater than for routine care (£90 v £425/patient/year).

Conclusion: These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population. Further studies are needed to elucidate whether this model of care is suitable for a larger population.

A cross-sectional study that applied the technology-acceptance model through a self-completed questionnaire, which was administered to a convenience sample of 125 outpatients attending outpatient anticoagulation services at a district general hospital in London, UK. Data were analyzed using descriptive statistics, factor analyses, and structural equation modeling.

Results

The participants were mainly male (64%) and aged ≥ 71 years (60%). All these patients were attending the hospital outpatient anticoagulation clinic for INR testing; only two patients were currently using INR self-testing, 84% of patients had no knowledge about INR self-testing using a portable coagulometer device, and 96% of patients were never offered the option of the INR self-testing. A significant structural equation model explaining 79% of the variance in patients’ intentions to use INR self-testing was observed. The significant predictors that directly affected patients’ intention to use INR self-testing were the perception of technology (β = 0.92, P < 0.001), trust in doctor (β = −0.24, P = 0.028), and affordability (β = 0.15, P = 0.016). In addition, the perception of technology was significantly affected by trust in doctor (β = 0.43, P = 0.002), age (β = −0.32, P < 0.001), and affordability (β = 0.23, P = 0.013); thereby, the intention to use INR self-testing was indirectly affected by trust in doctor (β = 0.40), age (β = −0.29), and affordability (β = 0.21) via the perception of technology.

Conclusion

Patients’ intentions to use portable coagulometers for INR self-testing are affected by patients’ perceptions about the INR testing device, the cost of device, trust in doctors/clinicians, and the age of the patient, which need to be considered prior to any intervention involving INR self-testing by patients. Manufacturers should focus on increasing the affordability of INR testing devices for patients’ self-testing and on the potential role of medical practitioners in supporting use of these medical devices as patients move from hospital to home testing.

International normalized ratio (INR) self-testing can improve the management of anticoagulation therapy with warfarin for the patients following mechanical heart valve replacement. Several reviews and studies have demonstrated self-management as an option to improve patient’s outcome considerably after mechanical heart valve replacement. We sought to analyze the security, economy and discuss the prospect of self-testing of anticoagulation therapy in patients following mechanical heart valve replacement in China, and evaluate the accuracy and stability of CoaguChek XS portable INR-testing device.

Methods

This was a prospective self-controlled clinical study conducted with 526 patients receiving oral warfarin anticoagulation therapy after mechanical heart valve replacement in the period of Mar.1, 2012 – Nov.1, 2012 in Cardiovascular Surgery Department of West China Hospital of Sichuan University. The same patient performed INR testing with CoaguChek XS portable coagulometer (group1) and central lab (group 2) in parallel. The follow-up time was 6 months. Meanwhile, a questionnaire was handed out to survey the expenses required for the re-examination visits to the hospital, time, and anticoagulation complications.

Results

No severe anticoagulation complications occurred in all the patients. No significant difference of the INR results were observed between group 1 and group 2, they showed significant relevance, r = 0.953(p

Conclusions

Results of CoaguChek XS monitor are precise and have a good consistency and stability as compared with traditional laboratory testing. For the patients receiving anticoagulation therapy after mechanical heart valve replacement, the self-testing of anticoagulation therapy with portable coagulometer is a safe choice, and it has a promising future application in China.

To investigate the effectiveness of patient self-management (PSM) of anticoagulation using warfarin in a typical primary care site in Canada and to determine the feasibility of conducting a future large-scale trial in this setting.

Design

An 8-month pragmatic open-label randomized crossover trial.

Setting

A typical Canadian primary care practice in British Columbia.

Intervention

Patients were randomized to PSM or physician management for 4 months, after which allocation was reversed. The PSM group members were instructed to monitor their serum international normalized ratio (INR) at community laboratories and to adjust their warfarin doses independently using provided nomograms. Education on warfarin dose adjustment was limited to a single 15-minute office visit.

Main outcome measures

The primary outcome was the proportion of INR values in the therapeutic range among participants. Feasibility outcomes included proportion of eligible patients consenting, patients’ preference of management strategy, patients’ satisfaction, and visits or phone communication with physicians regarding dose adjustment. Safety outcomes included bleeding or thromboembolic events.

Results

Eleven patients completed the trial, contributing 99 patient-months of monitoring and providing 122 INR measures. The mean proportion of INR values in therapeutic range among subjects in the PSM and physician-management groups was 82% and 80%, respectively (P = .82). The improvement in patient satisfaction with PSM was not significant. Ten of the 11 patients preferred PSM to physician management and elected to continue with this strategy after study completion (P = .001). No calls or visits were made to the physician regarding dose adjustment during the PSM period. There were no episodes of major bleeding or thromboembolic events.

Conclusion

Patient self-management was not demonstrated to be superior to standard care, but was easily implemented and was the method preferred by patients. Our feasibility outcomes justify a larger trial and suggest that subject recruitment and protocol adherence would not pose barriers for such a study.

Patients taking anticoagulants orally over the long term have international normalized ratios (INRs) outside the individual therapeutic range more than one-third of the time. Improved anticoagulation control will reduce hemorrhagic and thromboembolic event rates. To gauge the potential effect of improved anticoagulation control, we undertook to determine the proportion of anticoagulant-associated events that occur when INRs are outside the therapeutic range.

Methods

We conducted a meta-analysis of all studies that assigned hemorrhagic and thromboembolic events in patients taking anticoagulants to discrete INR ranges. We identified studies using the MEDLINE (1966–2006) and EMBASE (1980–2006) databases. We included studies reported in English if the majority of patients taking oral anticoagulants had an INR range with a lower limit between 1.8 and 2 and an upper limit between 3 and 3.5, and their INR at the time of the hemorrhagic or thromboembolic event was recorded.

Results

The final analysis included results from 45 studies (23 that reported both hemorrhages and thromboemboli; 14 that reported hemorrhages only; and 8, thromboemboli only) involving a median of 208 patients (limits of interquartile range [25th–75th percentile] 131–523 subjects; total n = 71 065). Of these studies, 64% were conducted at community practices; the remainder, at anticoagulation clinics. About 69% of the studies were classed as having moderate or high quality. Overall, 44% (95% confidence interval [CI] 39%–49%) of hemorrhages occurred when INRs were above the therapeutic range, and 48% (95% CI 41%–55%) of thromboemboli took place when below it. The mean proportion of events that occurred while the patient's INR was outside the therapeutic range was greater for studies with a short mean follow-up (< 1 yr). Between-study heterogeneity was significant (p < 0.001).

Interpretation

Improved anticoagulation control could decrease the likelihood of almost half of all anticoagulant-associated adverse events.

During the past 2 decades, a paradigm shift in the management of oral anticoagulation therapy has occurred. A multidisciplinary approach has been used and has proved beneficial from both a cost and quality perspective. However, this approach to anticoagulation therapy is not well established in Saudi Arabia and the Middle East, and the traditional way of managing anticoagulation patients is still the mainstay of care. The Pharmacy Services Division (PSD) in collaboration with physician, nursing, and medical support enterprises at the Dhahran Health Center established the pharmacy-managed anticoagulation clinic (ACC).

Objective:

To describe the implementation process of the first pharmacist-managed anticoagulation clinic in the eastern province of Saudi Arabia and its impact on patient care.

Methods:

The PSD in collaboration with medical staff successfully created a care delivery model utilizing clinical pharmacists’ expertise to provide comprehensive anticoagulation management services at Saudi Aramco Medical Services Organization (SAMSO). Planning included analyzing existing practices, reviewing the relevant literature, obtaining physician input, formulating a business proposal, and developing clinical protocols and guidelines. Collaborative relationships were established with the center laboratory, scheduling services, and nursing and medical departments. Clinic services include patient assessment, anticoagulation monitoring, warfarin dosage adjustment, medication dispensing at the clinic, patient education, and feedback to referring physicians. Data (2 years before and after clinic inception) for all patients enrolled at the anticoagulation clinic were reviewed to evaluate the impact of the clinic on anticoagulation management, adverse events, and patient satisfaction.

Results:

A total of 578 patients were enrolled in the ACC. The total percentage of international normalized ratio (INR) within the target range was 59% versus 48% when compared to the previous traditional practice. The number of INR tests per patient dropped by 19%. Minor and major adverse events occurred in 10% and 1.5% of patients, respectively. Overall, the patients were very satisfied with the new clinic compared to the previous practice.

Conclusion:

Implementation of the pharmacist-managed ACC in the eastern province of Saudi Arabia had a positive impact on patient care based on the improvements in the number of patients whose INR was within therapeutic range and patient satisfaction scores.

Objective: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0–3.0 and to explore the relation between achieved INR control and clinical outcomes.

Results: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range.

Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

CoaguChek S (Roche Diagnostics, Canada) is a portable device designed to monitor international normalized ratio (INR) by capillary puncture. Although the device is used in pediatrics, no study has evaluated its validity in patients of this population.

OBJECTIVE:

To evaluate the validity of CoaguChek S as an in-home INR monitor in patients younger than 18 years of age.

METHODS:

Data were based on 129 INR pairs collected from nine patients younger than 18 years of age followed up at an anticoagulation clinic between March 1, 2000, and January 19, 2004. The INRs from both the laboratory and CoaguChek S were used to evaluate concordance between the two methods using the intraclass correlation coefficient.

RESULTS:

The overall intraclass correlation coefficient between the CoaguChek S and the laboratory was 0.75 (95% CI 0.66 to 0.82). On average, CoaguChek S underestimated INRs by 0.11±0.54 units compared with those of the laboratory. INRs of 3.5 units and higher obtained with CoaguChek S were, on average, 0.49±1.09 units higher than those obtained in the laboratory.

CONCLUSIONS:

CoaguChek S appears to be a valid instrument for in-home INR monitoring for most patients younger than 18 years of age, with INR targets of 2.0 to 3.0 followed up by an anticoagulant therapy clinic’s program. However, caution must be used when interpreting INRs higher than 3.5. Parents should perform a second test to confirm all CoaguChek S INR results higher than 4.0.

Anticoagulation management services (AMSs) are widely used for anticoagulation management in many countries. Our AMS is a pharmacist-run ambulatory clinic with a physician advisory committee that manages patients referred with complicated anticoagulation histories. This paper assesses the adequacy of anticoagulation, rates of anticoagulant-related events and associated health care resource utilization for patients before and after referral to our AMS.

Methods

Consecutive patients referred to the AMS with 4 months of prior anticoagulation management who also had anticoagulation management for 4 months within the AMS were included in the evaluation. The primary endpoint was adequacy of anticoagulation (target international normalized ratio [INR] ± 0.5). Secondary outcomes included adverse events requiring an emergency department (ED) visit or hospital stay. These were classified by International Classification of Diseases (ICD) codes as thromboembolic, hemorrhagic, or non-anticoagulant related. Health care system resource consumption data were collected as number of hours spent in an ED and hospitalization costs.

Results

A total of 125 patients were included: 57.6% were male, with a mean age of 62.9 (standard deviation [SD]) ± 15.0 years. Indications for warfarin therapy were atrial fibrillation (40.0%), mechanical valve replacement (24.0%) and venous thromboembolism (19.2%). The adequacy of anticoagulant control was significantly greater during AMS care compared with the period before referral; patients were in the target INR range 66.5% versus 48.8% of the time, respectively (95% confidence interval [CI] 13.4%–22.0%; p

Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital.

Methods

A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency.

Results

No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time was detected for junior physicians.

Conclusions

Implementation of an automated PHS-based text alert system did not adversely impact clinical or safety outcomes of patients on warfarin therapy. Approximately 80% immediate recognition of text alerts was achieved. The potential benefits of an automated PHS alert for senior physicians were demonstrated.

Anticoagulation management is currently performed through anticoagulation clinics or self-managed with or without the help of medical services. Homebound patients are a unique population that cannot utilize anticoagulation clinics or self-testing. Telephone-based anticoagulation management could be an alternative to the traditional methods of monitoring warfarin in this subgroup. The objective of this retrospective, observational study is to investigate the feasibility of warfarin management in homebound patients.

Methods

This study was performed through the use of telephone-based adjustments of warfarin dose based on an international normalized ratio (INR) result. Four hundred forty-eight homebound patients referred to the anticoagulation clinic at Staten Island University Hospital were visited at home by a phlebotomist; a blood sample was drawn for initial laboratory testing. A nurse practitioner then called the patient or designated person to relay the INR result and to direct dosage adjustment. INR results and dosage changes were entered into an electronic medical record and analyzed statistically.

Results

The mean percentage of INR values in range was 58.39%. The mean time when the INR was in the therapeutic range was 62.75%. The percent of patients who were therapeutically controlled decreased as the number of medications increased. The complication rate was 4% per patient year, with an equal distribution between bleeding and clotting. These values compared favorably to other studies in which monitoring was performed through anticoagulation clinics or self-monitoring. The cost per visit at our anticoagulation clinic was found to be approximately $300 compared with $82 when utilizing our homebound service.

Conclusion

Telephone-based management of warfarin therapy in the homebound setting is feasible. It can lower the cost of health care expenditures compared to other modalities of anticoagulation management.

International Normalized Ratio (INR) is a world-wide routinely used factor in the monitoring of oral anticoagulation treatment (OAT). However, it was reported that other factors, e. g. factor II, may even better reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for OAT monitoring. The primary purpose of this study was to characterize the associations of INR with other vitamin K-dependent plasma proteins in a heterogenous group of individuals, including healthy donors, patients on OAT and patients not receiving OAT. The study aimed also at establishing the influence of co-morbid conditions (incl. accompanying diseases) and co-medications (incl. different intensity of OAT) on INR.

Design and Methods

Two hundred and three subjects were involved in the study. Of these, 35 were normal healthy donors (group I), 73 were patients on medication different than OAT (group II) and 95 were patients on stable oral anticoagulant (acenocoumarol) therapy lasting for at least half a year prior to the study. The values of INR and activated partial thromboplastin time (APTT) ratio, as well as activities of FII, FVII, FX, protein C, and concentration of prothrombin F1+2 fragments and fibrinogen were obtained for all subjects. In statistical evaluation, the uni- and multivariate analyses were employed and the regression equations describing the obtained associations were estimated.

Results

Of the studied parameters, three (factors II, VII and X) appeared as very strong modulators of INR, protein C and prothrombin fragments F1+2 had moderate influence, whereas both APTT ratio and fibrinogen had no significant impact on INR variability. Due to collinearity and low tolerance of independent variables included in the multiple regression models, we routinely employed a ridge multiple regression model which compromises the minimal number of independent variables with the maximal overall determination coefficient. The best-fitted two-component model included FII and FVII activities and explained 90% of INR variability (compared to 93% in the 5-component model including all vitamin K-dependent proteins). Neither the presence of accompanying diseases nor the use of OAT nor any other medication (acetylsalicylic acid, statins, steroids, thyroxin) biased significantly these associations.

Conclusion

Among various vitamin K-dependent plasma proteins, the coagulation factors II, VII and X showed the most significant associations with INR. Of these variables, the two-component model, including factors II and VII, deserves special attention, as it largely explains the overall variability observed in INR estimates. The statistical power of this model is validated on virtue of the estimation that the revealed associations are rather universal and remain essentially unbiased by other compounding variables, including clinical status and medical treatment. Further, much broader population studies are needed to verify clinical usefulness of methods alternate or compounding to INR monitoring of OAT.

Until recently, Prothrombin Time/International Normalized Ratio (PT/INR) measurements have typically been used to monitor patients on warfarin through institutional laboratories via venous puncture. The Point-of-Care Testing (POCT) device has revolutionized the patient care process by allowing for laboratory testing outside of the central laboratory.

Objective:

To analyze humanistic and clinical outcomes in patients currently treated with warfarin and monitored through a pharmacist-managed anticoagulation clinic using point-of-care testing (POCT) device versus venipuncture within ambulatory care clinics at our institution.

Methods:

All patients currently treated with warfarin therapy who were managed by clinical pharmacists for anticoagulation monitoring at the Medical University of South Carolina (MUSC) Family Medicine Center and University Diagnostic Center, were enrolled. Patients were asked to complete a satisfaction survey regarding their anticoagulation monitoring. In addition, data related to emergency department (ED) visits, hospitalizations and percent of time in the INR therapeutic range for 6 months pre- and post-implementation of POCT device was collected. This information was obtained through an electronic patient information database, Oacis.

Results:

A total of 145 patients were included in the data collection from the two clinics. The majority (41%) of these patients were taking warfarin for atrial fibrillation. Satisfaction surveys were completed by 86 (59 %) of patients. The surveys revealed that POCT device was preferred over venipuncture in 95% of patients. Reasons for the preference included more face-to-face interaction, less wait time, less pain, less blood needed, and quicker results. Of the 145 patients who were included in the objective data analysis, no significant differences were found in the number of hospitalizations, ED visits, or percent of time in the INR therapeutic range pre- and post-implementation of POCT device.

Conclusion:

The results of this study demonstrate improvement in patient satisfaction with POCT compared to venipuncture, with limited value in clinical outcomes.

AIM: To determine the reliability of international normalised ratio (INR) measurement in primary care by practice nurses using near patient testing (NPT), in comparison with results obtained within hospital laboratories by varied methods. METHODS: As part of an MRC funded study into primary care oral anticoagulation management, INR measurements obtained in general practice were validated against values on the same samples obtained in hospital laboratories. A prospective comparative trial was undertaken between three hospital laboratories and nine general practices. All patients attending general practice based anticoagulant clinics had parallel INR estimations performed in general practice and in a hospital laboratory. RESULTS: 405 tests were performed. Comparison between results obtained in the practices and those in the reference hospital laboratory (gold standard), which used the same method of testing for INR, showed a correlation coefficient of 0.96. Correlation coefficients comparing the results with the various standard laboratory techniques ranged from 0.86 to 0.92. It was estimated that up to 53% of tests would have resulted in clinically significant differences (change in warfarin dose) depending upon the site and method of testing. The practice derived results showed a positive bias ranging from 0.28 to 1.55, depending upon the site and method of testing. CONCLUSIONS: No technical problems associated with INR testing within primary care were uncovered. Discrepant INR results are as problematic in hospital settings as they are in primary care. These data highlight the failings of the INR to standardise when different techniques and reagents are used, an issue which needs to be resolved. For primary care to become more involved in therapeutic oral anticoagulation monitoring, close links are needed between hospital laboratories and practices, particularly with regard to training and quality assurance.

Results: Over 1484 patient-years, computer assisted anticoagulation was uncontrolled in 38.3% of patients (INR < 2.0 or > 3.0). No significant differences in INR control were observed with respect to patient age (< 65, 65–75, and > 75 years), although to achieve adequate control of anticoagulation, the frequency of testing increased significantly with age. Annual risks of bleeding complications, thromboembolism, and stroke were 0.76%, 0.35%, and 0.84%, respectively. No significant differences in these events were observed between the three age groups studied. Patients who had thromboembolic events and haemorrhagic complications were significantly more likely to have been under-anticoagulated (INR < 2.0) and over-anticoagulated (INR > 3.0), respectively, at the time of their clinical event.

Conclusions: Computerised long term oral anticoagulation for NRAF in a community setting of elderly and diverse patients is safe and effective. Anticoagulation control, bleeding events, thromboembolic episodes, and stroke rates are directly comparable with those reported in major clinical trials. The authors therefore support the strategy of rate control with long term oral anticoagulation for NRAF in general clinical practice.

Point-of-care international normalized ratio (INR) monitoring devices simplify warfarin management by allowing selected patients to monitor their own therapy in their homes. Patient self-testing (PST) has been shown to improve the clinical outcomes of warfarin therapy compared to usual care.

Objective

To compare management of warfarin therapy using PST combined with online supervision by physicians via a custom system with usual warfarin management, which involved laboratory testing and physician dosing.

Methods

Interested patients were recruited via community pharmacies to participate in a warfarin PST training program. Participants were required to have a long-term indication for warfarin, have been taking warfarin for at least 6 months, and have Internet access in their home. The training involved two sessions covering theoretical aspects of warfarin therapy, use of the CoaguChek XS, and the study website. Following training, patients monitored their INR once weekly for up to 3 months. Patients and physicians utilized a secure website to communicate INR values, dosage recommendations, and clinical incidents. Physicians provided a 6-12 month history of INR results for comparison with study results. The percentage of time spent within the therapeutic INR range (TTR) was the primary outcome, with participants acting as their own historical controls. The percentage of INR tests in range and participant satisfaction were secondary outcomes.

Results

Sixteen patients completed training requirements. The mean age of participants was 69.8 (SD 10.1) years. TTR improved significantly from 66.4% to 78.4% during PST (P=.01), and the number of tests within the target range also improved significantly (from 66.0% at prior to the study to 75.9% during PST; P=.04). Patients and physicians expressed a high degree of satisfaction with the monitoring strategy and online system.

Conclusions

PST supported by an online system for supervision was associated with improved INR control compared to usual care in a small group of elderly patients. Further research is warranted to investigate the clinical outcomes and cost-effectiveness of online systems to support patients monitoring medications and chronic conditions in the home.

Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used.

Warfarin is an oral anticoagulant (OAT) that needs active management to ensure therapeutic range. Initial management is often carried out as an inpatient, though not requiring inpatient facilities. This mismatch results in financial costs which could be directed more efficaciously. The extent of this has previously been unknown. Here we aim to calculate the potential number of bed nights which may be saved among those being dose optimized as inpatients and examine associated factors.

Methods

A 6 week prospective audit of inpatients receiving OAT, at Cork University Hospital, was carried out. The study period was from 11th June 2007 to 20th July 2007. Data was collected from patient's medications prescription charts, medical record files, and computerised haematology laboratory records. The indications for OAT, the patient laboratory coagulation results and therapeutic intervals along with patient demographics were analysed. The level of potentially avoidable inpatient nights in those receiving OAT in hospital was calculated and the potential cost savings quantified. Potential avoidable bed nights were defined as patients remaining in hospital for the purpose of optimizing OAT dosage, while receiving subtherapeutic or therapeutic OAT (being titred up to therapeutic levels) and co-administered covering low molecular weight heparin, and requiring no other active care. The average cost of €638 was taken as the per night hospital stay cost for a non-Intensive Care bed. Ethical approval was granted from the Ethical Committee of the Cork Teaching Hospitals, Cork, Ireland.

Results

A total of 158 patients were included in the audit. There was 94 men (59.4%) and 64 women (40.6%). The mean age was 67.8 years, with a median age of 70 years.

It was confirmed that, there are potentially avoidable nights in patients receiving OAT. The majority of this group were those being commenced on OAT for the first time (p = 0.00002), in the specialities of Cardiology, Cardiothoracic surgery and Care of the Elderly. The potential number of bed nights to be saved is 13 per week for the hospital or 1.1 bed nights per 10,000 general hospital admissions. These were predominantly weekday nights. The estimated cost of avoidable inpatient OAT dose optimization was approximately €8300 per week.

Conclusion

With rising costs and the increasing demands for acute hospital beds, alterations to inpatient management for this group of patients should be considered. Alternatives include increasing the size of current anticoagulation clinics, introduction of POCT (point of care testing) devices and increased GP management. POCT can be justified based upon the publication by Gardiner et al, who showed that 87% of patients find self testing straightforward, 87% were confident in the result they obtained using the devices and 77% preferred self testing.